This research program to examine the structure of the major histocompatibility complex in rats and its effects on immunological functions has focused on five areas. First, serological and CML mapping of the second class I locus (RT1.E) and the orientation of the loci controlling cell surface antigens and enzymes have given a detailed map of the MHC. Second, 25 hybridomas have been made against antigens controlled by the MHC. They will be used to isolate the antigens for biochemical study by peptide mapping. Preliminary studies have shown that three of these myelomas isolate unique class I MHC antigens. Third, a considerable amount of work on the biological effects of MHC antigens has come to fruition, including studies on heart, research on skin and bone marrow and studies on cellular immunity to Listeria monocytogenes. The relative effects of MHC and non-MHC genes were explored by using our congenic and recombinant animals. We also demonstrated sequential changes in the expression of cell surface alloantigens on erythrocytes after bone marrow grafting without other hematological changes. We have demonstrated, for the first time, that the ability of cyclosporin A to prolong a graft is genetically controlled. Different types of genetic control are involved in delayed hypersensitivity, response to soluble and particulate antigens and resistence to microbial infection with Listeria. Fourth, we have demonstrated genetically controlled polymorphisms in six proteins and the lack of polymorphism in the Ah phenotype, which regulates susceptibility to aryl hydrocarbons. Finally, we have been developing somatic cell hybridization for cytogenetic studies to localize the chromosome which carries the MHC and, eventually, other markers in the rat genome.